Chemistry:HL156A
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| Other names | IM156, HL271 acetate, UNII-4G3BUV6ZSK |
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| Formula | C13H16F3N5O |
| Molar mass | 315.300 g·mol−1 |
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HL156A is a derivative of metformin and a potent oxidative phosphorylation inhibitor and AMP-activated protein kinase activating biguanide.[1][2] Certain types of cancer cells requires oxidative phosphorylation to survive. By targeting it, HL156A might help in improving anticancer therapy.[3] It is more potent than acadesine or metformin at activating AMP-activated protein kinase.[2] It is synthesized by Hanall Biopharma.[4]
Medical uses
It is in phase 1 trial in patients with advanced solid tumor and lymphoma.[5][1]
Pharmacology
 | This section is missing information about how the AMP-activated protein kinase effect translates to oxidative phosphorylation inhibition; whether these extra effects are downstream or independent of AMPK; whether a direct target is known (AMPK is not the direct target for metformin). (July 2022) |
Apart from AMP-activated protein kinase activation, it also inhibits expression and activation of insulin-like growth factor-1, protein kinase B, mammalian target of rapamycin (mTOR), and extracellular signal-regulated kinases.[6][7]
Research
It is researched in multiple conditions like liver and renal fibrosis,[2][8] cancer[6][9] and drug resistance in cancer.[7] HL176OUT04, a drug with similar pharmacology, has been also developed.[10]
See also
References
- ↑ 1.0 1.1 "Phase I study of IM156, a novel potent biguanide oxidative phosphorylation (OXPHOS) inhibitor, in patients with advanced solid tumors.". Journal of Clinical Oncology 38 (15_suppl): 3590. 2020. doi:10.1200/JCO.2020.38.15_suppl.3590. ISSN 0732-183X.
- ↑ 2.0 2.1 2.2 "HL156A, a novel pharmacological agent with potent adenosine-monophosphate-activated protein kinase (AMPK) activator activity ameliorates renal fibrosis in a rat unilateral ureteral obstruction model". PLOS ONE 13 (8): e0201692. 2018. doi:10.1371/journal.pone.0201692. PMID 30161162. Bibcode: 2018PLoSO..1301692T.
- ↑ "Why All the Fuss about Oxidative Phosphorylation (OXPHOS)?". Journal of Medicinal Chemistry 63 (23): 14276–14307. December 2020. doi:10.1021/acs.jmedchem.0c01013. PMID 33103432.
- ↑ "HL156A, a novel AMP-activated protein kinase activator, is protective against peritoneal fibrosis in an in vivo and in vitro model of peritoneal fibrosis". American Journal of Physiology. Renal Physiology 310 (5): F342–F350. March 2016. doi:10.1152/ajprenal.00204.2015. PMID 26661649.
- ↑ "A Multi Center, Open-label, Phase 1 Clinical Trial to Evaluate the Safety, Tolerability, and Preliminary Efficacy of IM156 in Patients with Advanced Solid Tumors and Lymphoma". 15 October 2020. https://clinicaltrials.gov/ct2/show/NCT03272256.
- ↑ 6.0 6.1 "New metformin derivative HL156A prevents oral cancer progression by inhibiting the insulin-like growth factor/AKT/mammalian target of rapamycin pathways". Cancer Science 109 (3): 699–709. March 2018. doi:10.1111/cas.13482. PMID 29285837.
- ↑ 7.0 7.1 "Metformin Derivative HL156A Reverses Multidrug Resistance by Inhibiting HOXC6/ERK1/2 Signaling in Multidrug-Resistant Human Cancer Cells". Pharmaceuticals 13 (9): 218. August 2020. doi:10.3390/ph13090218. PMID 32872293.
- ↑ "AMP-activated protein kinase activator, HL156A reduces thioacetamide-induced liver fibrosis in mice and inhibits the activation of cultured hepatic stellate cells and macrophages". International Journal of Oncology 49 (4): 1407–1414. October 2016. doi:10.3892/ijo.2016.3627. PMID 27498767.
- ↑ "Inhibiting stemness and invasive properties of glioblastoma tumorsphere by combined treatment with temozolomide and a newly designed biguanide (HL156A)". Oncotarget 7 (40): 65643–65659. October 2016. doi:10.18632/oncotarget.11595. PMID 27582539.
- ↑ Hyeonsang S (2016). The AMPK activators, HL156A and HL176OUT04 reduce thioacetamide-induced hepatic fibrosis via the inhibition of hepatic stellate cell activation (Ph.D. thesis). 서울대학교 융합과학기술대학원 (Seoul National University Graduate School of Convergence Science and Technology). hdl:10371/133411.
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